Please use this identifier to cite or link to this item: https://doi.org/10.1182/blood-2009-02-204818
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dc.titleExpression profiling of a hemopoietic cell survival transcriptome implicates osteopontin as a functional prognostic factor in AML
dc.contributor.authorPowell, J.A.
dc.contributor.authorThomas, D.
dc.contributor.authorBarry, E.F.
dc.contributor.authorKok, C.H.
dc.contributor.authorMcClure, B.J.
dc.contributor.authorTsykin, A.
dc.contributor.authorTo, L.B.
dc.contributor.authorBrown, A.
dc.contributor.authorLewis, I.D.
dc.contributor.authorHerbert, K.
dc.contributor.authorGoodall, G.J.
dc.contributor.authorSpeed, T.P.
dc.contributor.authorAsou, N.
dc.contributor.authorJacob, B.
dc.contributor.authorOsato, M.
dc.contributor.authorHaylock, D.N.
dc.contributor.authorNilsson, S.K.
dc.contributor.authorD'Andrea, R.J.
dc.contributor.authorLopez, A.F.
dc.contributor.authorGuthridge, M.A.
dc.date.accessioned2014-11-26T09:59:39Z
dc.date.available2014-11-26T09:59:39Z
dc.date.issued2009-11-26
dc.identifier.citationPowell, J.A., Thomas, D., Barry, E.F., Kok, C.H., McClure, B.J., Tsykin, A., To, L.B., Brown, A., Lewis, I.D., Herbert, K., Goodall, G.J., Speed, T.P., Asou, N., Jacob, B., Osato, M., Haylock, D.N., Nilsson, S.K., D'Andrea, R.J., Lopez, A.F., Guthridge, M.A. (2009-11-26). Expression profiling of a hemopoietic cell survival transcriptome implicates osteopontin as a functional prognostic factor in AML. Blood 114 (23) : 4859-4870. ScholarBank@NUS Repository. https://doi.org/10.1182/blood-2009-02-204818
dc.identifier.issn00064971
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/110738
dc.description.abstractDeregulated cell survival programs are a classic hallmark of cancer. We have previously identified a serine residue (Ser585) in the βc subunit of the granulocyte-macrophage colony-stimulating factor receptor that selectively and independently promotes cell survival. We now show that Ser585 phosphorylation is constitutive in 20 (87%) of 23 acute myeloid leukemia (AML) patient samples, indicating that this survivalonly pathway is frequently deregulated in leukemia. We performed a global expression screen to identify gene targets of this survival pathway and report a 138-gene βc Ser585-regulated transcriptome. Pathway analysis defines a gene network enriched for PI3-kinase target genes and a cluster of genes involved in cancer and cell survival. We show that one such gene, osteopontin (OPN), is a functionally relevant target of the Ser585-survival pathway as shown by siRNA-mediated knockdown ofOPN expression that induces cell death in both AML blasts and CD34+CD38+CD123+ leukemic progenitors. Increased expression of OPN at diagnosis is associated with poor prognosis with multivariate analysis indicating that it is an independent predictor of overall patient survival in normal karyotype AML (n = 60; HR = 2.2; P = .01). These results delineate a novel cytokine-regulated Ser585/ PI3-kinase signaling network that is deregulated in AML and identify OPN as a potential prognostic and therapeutic target. © 2009 by The American Society of Hematology.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1182/blood-2009-02-204818
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.description.doi10.1182/blood-2009-02-204818
dc.description.sourcetitleBlood
dc.description.volume114
dc.description.issue23
dc.description.page4859-4870
dc.description.codenBLOOA
dc.identifier.isiut000272190700015
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